Cysteine S-glycosylation, a new post-translational modification found in glycopeptide bacteriocins

O-glycosylation is a ubiquitous eukaryotic post-translational modification, whereas early reports of S-linked glycopeptides have never been verified. Prokaryotes also glycosylate proteins, but there are no confirmed examples of sidechain glycosylation in ribosomal antimicrobial polypeptides collectively known as bacteriocins. Here we show that glycocin F, a bacteriocin secreted by Lactobacillus plantarum KW30, is modified by an N-acetylglucosamine β-O-linked to Ser18, and an N-acetylhexosamine S-linked to C-terminal Cys43. The O-linked N-acetylglucosamine is essential for bacteriostatic activity, and the C-terminus is required for full potency (IC₅₀ 2 nM). Genomic context analysis identified diverse putative glycopeptide bacteriocins in Firmicutes. One of these, the reputed lantibiotic sublancin, was shown to contain a hexose S-linked to Cys22.     

Extra-Lysosomal Localization of Arylsulfatase B in Human Colonic Epithelium

The enzyme arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB; ASB) removes 4-sulfate groups from the sulfated glycosaminoglycans (sGAG) chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Inborn deficiency of ARSB leads to the lysosomal storage disease mucopolysaccharidosis VI, characterized by accumulation of sGAG in vital organs, disruption of normal physiological processes, severe morbidity, and premature death. Recent published work demonstrated extra-lysosomal localization with nuclear and cell membrane ARSB observed in bronchial and colonic epithelial cells, cerebrovascular cells, and hepatic cells. In this report, the authors present ARSB immunostaining in a colonic microarray and show differences in distribution, intensity, and pattern of ARSB staining among normal colon, adenomas, and adenocarcinomas. Distinctive, intense luminal membrane staining was present in the normal epithelial cells but reduced in the malignancies and less in the grade 3 than in the grade 1 adenocarcinomas. In the normal cores, a distinctive pattern of intense cytoplasmic positivity at the luminal surface was followed by reduced staining deeper in the crypts. ARSB enzymatic activity was significantly greater in normal than in malignant tissue. These study findings affirm extra-lysosomal localization of ARSB and suggest that altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue.     

The acquisition of antigen cross-presentation function by newly formed dendritic cells

The development of Ag-presenting functions by murine dendritic cells (DCs) of the CD8(+) DC lineage was studied using a Flt-3 ligand stimulated bone-marrow culture system. Although newly formed DCs of this lineage are capable of Ag uptake and efficient presentation to T cells on MHC class II, they initially lack the ability to cross-present exogenous Ags on MHC class I. Cross-presentation capacity is acquired as a subsequent maturation step, promoted by cytokines such as GM-CSF. The development of cross-presentation capacity by the DCs in these cultures may be monitored by the parallel development of DC surface expression of CD103. However, the expression of CD103 and cross-presentation capacity are not always linked; therefore, CD103 is not an essential part of the cross-presentation machinery. These results explain the considerable variability in CD103 expression by CD8(+) DCs as well as the findings that not all DCs of this lineage are capable of cross-presentation.     

Modelling the epidemiology of hepatitis B in New Zealand

Hepatitis B is a vaccine preventable disease caused by the hepatitis B virus (HBV) that can induce potentially fatal liver damage. It has the second highest mortality rate of all vaccine preventable diseases in New Zealand. Vaccination against HBV was introduced in New Zealand in 1988, and the country is now categorised with overall low endemicity but with areas of both high and medium endemic levels. We present an SECIR compartmental mathematical model, with the population divided into age classes, for the transmission of HBV using local data on incidence of infection and vaccination coverage. We estimate the basic reproduction number, R₀, to be 1.53, and show that the vaccination campaign has substantially reduced this below one. However, a large number of carriers remain in the population acting as a source of infection.     

Which are the phenologically flexible species? A case study with common passerine birds

One of the most consensual ecological effects of the current climate warming is the alteration of the environmental timing of ecosystems. Phenological shifts, at different levels of food webs, are predicted to have major effects on species assemblages. Indeed it is unlikely that all species should be able to respond to the phenological shifts of their environment evenly. Yet questions remain about the specific traits that predict the ability of a species to track the temporal fluctuations of its environment. In this study, we use data from the French Constant Effort Site ringing program over a 20 years period (1989–2008) to estimate the ability of 20 common passerine species to adjust their breeding phenology to spring temperature variations. We show that the sensitivity of species breeding phenology to climate relates to species mean migration distance, species’ thermal and habitat niche breadth and brain mass. Species with the broadest ecological and thermal niches, the shortest mean migration distances and the largest brains were most able to adjust their breeding phenology to temperature variations. Our results thus identify long distance migrants and ecological specialists as species that could most suffer from the future expected climate change and suggests phenological adjustment as one possible mechanism underlying the replacement of specialist species by more generalist ones, the so called functional biotic homogenization.     

Military nutrition: maintaining health and rebuilding injured tissue

Food and nutrition are fundamental to military capability. Historical examples demonstrate that a failure to supply adequate nutrition to armies inevitably leads to disaster; however, innovative measures to overcome difficulties in feeding reap benefits, and save lives. In barracks, UK Armed Forces are currently fed according to the relatively new Pay As You Dine policy, which has attracted criticism from some quarters. The recently introduced Multi-Climate Ration has been developed specifically to deal with issues arising from Iraq and the current conflict in Afghanistan. Severely wounded military personnel are likely to lose a significant amount of their muscle mass, in spite of the best medical care. Nutritional support is unable to prevent this, but can ameliorate the effects of the catabolic process. Measuring and quantifying nutritional status during critical illness is difficult. A consensus is beginning to emerge from studies investigating the effects of nutritional interventions on how, what and when to feed patients with critical illness. The Ministry of Defence is currently undertaking research to address specific concerns related to nutrition as well as seeking to promote healthy eating in military personnel.     

Dispersion statistics and a sampling plan for Helicoverpa (Lepidoptera: Noctuidae) on fresh-market tomatoes (Lycopersicon esculentum)

Abstract  Helicoverpa spp. is the primary pest in the Australian fresh-market tomato industry. We describe the spatial distribution of Helicoverpa spp. eggs on fresh-market tomato crops in the Goulburn Valley region of Victoria, and present a sequential sampling plan for monitoring population densities. The distribution of Helicoverpa spp. eggs was highly contagious, as indicated by a Taylor's b -value of 1.59. This high level of contagion meant that relatively large sample sizes would need to be collected to obtain an estimate of population density. High-precision sampling plans generally necessitated impractical sample sizes, and thus the plan we present is a relatively low-precision level plan (SE/mean = 0.3). Nonetheless, this level of precision is considered adequate for most agronomic scenarios. The plan was validated using a statistical re-sampling approach. The level of precision achieved was generally close to the nominal level. Likewise, the number of samples collected generally showed little departure from the theoretically calculated minimum sample size.     

Regulatory T cells are resistant to apoptosis via TCR but not P2X7

Regulatory T cells (Tregs) are relatively autoreactive yet, paradoxically, have been found to display normal sensitivity to thymic deletion. The relationship between self-avidity, apoptosis, and the selection of Tregs therefore remains unclear. We show that thymic Tregs develop efficiently, even at low self-avidity, and are moderately resistant to apoptosis in comparison to conventional thymocytes. Consistent with this, although conventional self-reactive T cell populations undergo chronic peripheral deletion, self-reactive Tregs are largely spared removal. Similarly, the distribution of Tregs among peripheral CD4(+) cells exhibits a linear inverse relationship with CD45RB expression, indicating relative apoptosis resistance of Tregs in chronic responses to environmental Ags. We also show that appropriate controls for CD45RB levels are important for comparisons of Treg and conventional T cell activity. When thus controlled, and contrary to previous reports, Tregs exhibit normal sensitivity to cell death through TCR-independent stimuli, such as the purinergic receptor, P2X(7). Finally, although absence of CD45 in gene-targeted mice results in profound T cell hyporesponsiveness, there is little or no effect on thymic Treg frequency. In summary, the data support a model in which signal strength plays little part in Treg lineage specification, though moderate resistance of self-reactive Tregs to apoptosis may result in progressive biasing of peripheral Treg TCRs toward autoreactivity in comparison to those of conventional T cells.     

Resemblance for age at menarche in female twins reared apart and together

Menarche is a significant developmental event in the lives of young females. Genetic and family environmental influences on the timing of its occurrence are explored in the first formal analysis using reared-apart and reared-together monozygotic (MZA, MZT) and dizygotic (DZA, DZT) twin pairs. Mean age at menarche was 12.50 years (SD = 1.67) for the reared-apart pairs and 12.86 years (SD = 1.49) for the reared-together pairs. Intraclass correlations for age at menarche were 0.56 for MZA twins, 0.16 for DZA twins, 0.70 for MZT twins, and 0.41 for DZT twins. The mean within-pair difference was 1.07 years (SD = 1.04) for MZA twins, 1.67 years (SD = 1.59) for DZA twins, 0.64 year (SD = 0.86) for MZT twins, and 1.43 years (SD = 1.34) for DZT twins. These results are consistent with genetic influence, although the lower correlations for reared-apart twins and their larger within-pair differences suggest that age at menarche is partly affected by common rearing environments. Feeling understood by one's father during the growing-up years was significantly associated with earlier age at menarche, and a comparable trend was found for feeling understood by one's mother. These findings are considered with reference to current theories of pubertal timing.     

Identification of Pseudomonas syringae pv. syringae 61 type III secretion system Hrp proteins that can travel the type III pathway and contribute to the translocation of effector proteins into plant cells

Pseudomonas syringae translocates effector proteins into plant cells via an Hrp1 type III secretion system (T3SS). T3SS components HrpB, HrpD, HrpF, and HrpP were shown to be pathway substrates and to contribute to elicitation of the plant hypersensitive response and to translocation and secretion of the model effector AvrPto1.